Personalizing dry eye treatment by addressing disease at its source

In the ocular surface disease (OSD) community, there is a growing consensus that diagnoses should be specific regarding etiology and that treatments should be personalized to account for each patient’s underlying cause, environmental factors, and disease stage.¹ Traditionally, dry eye disease (DED) has been treated with anti-inflammatory eye drops such as cyclosporine, lifitegrast (Xiidra; Bausch + Lomb), and corticosteroids.

However, in many cases, the loss of tear film homeostasis is the initiating factor that leads to chronic inflammation and damage to the ocular surface.² The tear film imbalance may be due to evaporative dry eye from meibomian gland dysfunction (MGD), autoimmune disease, or corneal trauma related to surgery or contact lens wear. In such cases, treating inflammation is important, but it is also important to address the underlying disease processes that led to the loss of homeostasis and inflammation. Recent innovations in the DED marketplace, including but not limited to perfluorohexyloctane (Miebo; Bausch + Lomb), lotilaner (Xdemvy; Tarsus Pharmaceuticals), varenicline (Tyrvaya; Viatris), and acoltremon (Tryptyr; Alcon), have expanded the ability to personalize care for patients with OSD, based on which aspects of the tear film are most affected. Further innovations continue to expand clinical knowledge of the ocular surface and to provide novel mechanisms for addressing the root cause.

In the context of an increasingly active late-stage pipeline, this article concentrates on 2 investigational agents that may address the underlying disease pathology.

Targeting the root cause of MGD

Although perfluorohexyloctane eye drops mimic some functions of natural meibum to inhibit tear evaporation, meibomian gland pathology remains a challenge. This is where selenium sulfide ointment (AZR-MD-001; Azura Ophthalmics), a first-in-class keratolytic and lipogenic agent,³ could make a difference. Building on lessons from dermatology, where keratolytics are used to treat certain types of acne and seborrheic dermatitis,^4,5 AZR-MD-001 is applied to the eyelids twice a week to break up the accumulated keratin that can block meibomian gland orifices. Once the keratin is softened, the active ingredient also reaches the meibomian glands and enhances lipid production, restoring clear oil flow.^3,6,7 The drug is intended to address the pathophysiology of MGD (and contact lens discomfort).

According to published results of a phase 2 trial (NCT03652051), patients using the 0.5% ointment achieved a statistically significant increase from baseline in the number of meibomian glands yielding liquid secretion (MGYLS) compared with vehicle, as well as significant improvements in the meibomian gland secretion (MGS) score, tear breakup time, and Ocular Surface Disease Index (OSDI) scores.³ In pooled results from phase 2 and 3 studies, participants treated with AZR-MD-001 were more likely than those treated with vehicle to achieve an increase of greater than or equal to 3 MGYLS,⁷ a level of change associated with improved signs and symptoms of dry eye. To be enrolled in these studies, participants had to have a baseline MGS score of 12 or less (out of a possible 45 for the lower lid) and an OSDI score of 13 to 34, indicative of mild to moderate dry eye. A new drug application for AZR-MD-001 is likely to be filed with the FDA in 2026, according to Azura Ophthalmics.⁸

Targeting the root cause of epithelial damage and inflammation

Vezocolmitide (ST-100; Stuart Therapeutics) is a collagen mimetic peptide (CMP) therapy designed to seek out and repair damaged collagen, thereby improving the health of the epithelium and restoring ocular surface health by promoting the release of stabilizing growth factors.⁹

Collagen is present in various forms throughout the cornea. For example, the basement membrane that holds the corneal epithelium in place is composed primarily of type IV collagen.¹⁰ When the epithelium breaks down (as occurs with tear film degradation in DED), the exposed collagen beneath can fragment, further contributing to epithelial instability, sustained inflammation, and impaired healing.^10,11 Unfortunately, collagen is replaced slowly, especially in the absence of a healthy tear milieu, which contributes to poor healing in all kinds of OSDs. By targeting fragmented collagen and repairing its helical structure, CMP therapy can speed this process. This mechanism of action is why clinical trials of ST-100 have demonstrated changes in corneal surface staining: The drug is intended to heal corneal tissue rather than affect specific layers of the tear film.

In a phase 2 trial (NCT05241470), vezocolmitide demonstrated clinically relevant reductions in corneal staining, especially in the central and inferior cornea.⁹ It was well tolerated, with an adverse event rate similar to that of vehicle. More recently, a phase 3a trial (NCT06178679) achieved statistically significant week 1 fluorescein staining improvement with clinically meaningful (> 20%) improvement on day 4.¹² Statistically significant visual function improvement (change in multiple DED symptoms on a visual analog scale) relative to placebo was achieved on day 2. Among the patients with the most severe DED—those who were sensitive to a controlled adverse environment challenge—61% had clinically meaningful improvements in central corneal staining, with improvement seen as early as day 2. The clinically meaningful (> 20%)¹³ magnitude of stain improvement vs vehicle seen in the study was encouraging.¹² The rapid impact on signs and symptoms is also encouraging, because there is often a delay of weeks or months before patients experience relief with current therapies.^14,15

CMP therapy may be helpful for a wide range of patients with DED and particularly for those with stubborn superficial punctate keratitis (SPK) and/or those with early-stage neurotrophic keratitis (NK). There is significant overlap between DED and stage I NK. John Hovanesian, MD, recently showed that more than half of patients with DED presenting for cataract surgery had stage I NK.¹⁶ Although this was a small (n = 31), single-center study, it suggests that early-stage NK is more common than many clinicians realize.

Although these patients might not complain of significant discomfort, clinical examination reveals staining and epithelial breakdown that may affect surgical outcomes but cannot be effectively addressed with anti-inflammatory therapy. Nerve growth factor treatment such as cenegermin-bkbj (Oxervate; Dompé Pharmaceuticals) can of course be considered in such patients, but additional options would be valuable. Phase 3b safety and efficacy studies of ST-100 for DED will begin later this year, according to the company’s website (https://stuarttherapeutics.com/clinical-trials/). Beyond DED, CMP therapy may have potential for corneal wound healing post trauma or postsurgical procedures, for treating persistent epithelial defects, and for later-stage NK. Preclinical work for a number of other indications is ongoing, according to the company’s website (https://stuarttherapeutics.com/our-pipeline/).

The DED pipeline is large and growing. The investigational drugs discussed here are just 2 of many, but they are featured here not only because they could be available in clinical practice soon, but also because they represent unique treatment pathways and opportunities to address the root causes of DED for the benefit of patients.

Marjan Farid, MD
E: [email protected]

Farid is director of cornea, cataract, and refractive surgery and a clinical professor at the UCI Gavin Herbert Eye Institute in California. She is a consultant/adviser for AbbVie, Alcon Laboratories, Allergan, Aurion, Bausch + Lomb, Bio-Tissue, BVI, Carl Zeiss Meditec, CorneaGen, Glaukos, Harrow, Johnson & Johnson Vision, Orasis Pharmaceuticals, Sight Sciences, Sun Ophthalmics, Stuart Therapeutics, Tarsus Pharmaceuticals, and Viatris.

References

1. Jones L, Craig JP, Markoulli M, et al. TFOS DEWS III: management and therapy. Am J Ophthalmol. 2025;279:289-386. doi:10.1016/j.ajo.2025.05.039

2. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and classification report. Ocul Surf. 2017;15(3):276-283. doi:10.1016/j.jtos.2017.05.008

3. Watson SL, Jones LW, Stapleton F, et al. Efficacy and safety of AZR-MD-001 sele­nium sulfide ophthalmic ointment in adults with meibomian gland dysfunction: a vehicle-controlled, randomized clinical trial. Ocul Surf. 2023;29:537-546. doi:10.1016/j.jtos.2023.07.002

4. Dall'Oglio F, Nasca MR, Gerbino C, Micali G. An overview of the diagnosis and management of seborrheic dermatitis. Clin Cosmet Investig Dermatol. 2022;15:1537-1548. doi:10.2147/CCID.S284671

5. Debevec-McKenney E, Syrnioti A, Mauldin A, Lee JH. Keratolytics: nursing pharmacology. Osmosis from Elsevier; 2022. Accessed July 7, 2026. https://www.osmosis.org/learn/es/Keratolytics:_Nursing_Pharmacology

6. Alster Y, Epstein-Barash H, Rapaport H, Rafaeli O. Lipogenic activity of selenium disulfide and its role in enhancing lipid production in meibomian glands. Invest Ophthalmol Vis Sci. 2021;62:693.

7. Nichols KK, Jones L, Schallhorn J, et al. AZR-MD-001 0.5% significantly improves meibomian glands yielding liquid secretions with clinically meaningful benefit across the dry eye disease spectrum. Presented at: Association for Research in Vision and Ophthalmology Annual Meeting; May 3-7, 2026; Denver, CO.

8. Azura Ophthalmics corporate update: AZR-MD-001 NDA submission expected in 2H 2026. News release. Azura Ophthalmics; December 10, 2025. Accessed July 6, 2026. https://azuraophthalmics.com/press-releases/azura-ophthalmics-corporate-update-azr-md-001-nda-submission-expected-in-2h-2026/

9. Baratta RO, Schlumpf E, Del Buono BJ, DeLorey S, Ousler G, Calkins DJ. A phase 2 trial to test safety and efficacy of ST-100, a unique collagen mimetic peptide ophthalmic solution for dry eye disease. Ophthalmol Sci. 2023;4(3):100451. doi:10.1016/j.xops.2023.100451

10. Baratta RO, Schlumpf E, Buono BJD, DeLorey S, Calkins DJ. Corneal collagen as a potential therapeutic target in dry eye disease. Surv Ophthalmol. 2022;67(1):60-67. doi:10.1016/j.survophthal.2021.04.006

11. Moussa SM, Mahmoud SS, Aly EM, Talaat MS. Bio-spectroscopic analysis of corneal structural alterations in dry eye disease: a study of collagen, co-enzymes, lipids, and proteins with emphasis on phytotherapy intervention. Int J Biol Macromol. 2024;280(pt 3):136010. doi:10.1016/j.ijbiomac.2024.136010

12. Luchs J, Del Buono BJ, DeLorey S, Schlumpf E. A randomized double-masked vehicle controlled multi-center phase 3a dry eye disease (DED) trial to test safety and efficacy of ST-100, a collagen mimetic peptide therapeutic. Presented at: Association for Research in Vision and Ophthalmology Annual Meeting; May 3-7, 2026; Denver, CO.

13. Akpek EK, Sheppard JD, Krösser S. Corneal staining responder analysis: a clinically meaningful dry eye outcome. Ophthalmology. 2025;132(12):1335-1341. doi:10.1016/j.ophtha.2025.07.015

14. de Oliveira RC, Wilson SE. Practical guidance for the use of cyclosporine ophthalmic solutions in the management of dry eye disease. Clin Ophthalmol. 2019;13:1115-1122. doi:10.2147/OPTH.S184412

15. White DE, Zhao Y, Jayapalan H, Machiraju P, Periyasamy R, Ogundele A. Treatment satisfaction among patients using anti-inflammatory topical medications for dry eye disease. Clin Ophthalmol. 2020;14:875-883. doi:10.2147/OPTH.S233194

16. Hovanesian JA. The THINK study: testing hypoesthesia and the incidence of neurotrophic keratopathy in cataract patients with dry eye. Clin Ophthalmol. 2024;18:3627-3633. doi:10.2147/OPTH.S501452